VERU-111 in the Treatment of SARS-Cov-2 Infection by Assessing Its Effect on the Proportion of Patients Who Die on Study

SARS-CoV Infection Clinical Trial

— VERU-111  

Official title:

Phase 3, Randomized, Placebo-Controlled, Efficacy and Safety Study of VERU-111 for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Patients at High Risk for Acute Respiratory Distress Syndrome (ARDS).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04842747
• Other study ID #: V3011902
• Status: Completed
• Phase: Phase 3
• Start date: May 18, 2021
• Est. completion date: July 6, 2022

Study information

• Verified date: March 2023
• Source: Veru Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To demonstrate the efficacy of VERU-111 in the treatment of SARS-Cov-2 Infection by assessing its effect on the proportion of patients who die on study (prior to Day 60).

Description:

This study is a multicenter, randomized, placebo-control, efficacy and safety study of VERU-111 for the treatment of COVID-19. Subjects will receive either 9mg of VERU-111 or matching placebo orally or through nasogastric tube daily for up to 21 days or until the subject is discharged from the hospital, whichever comes first. The primary efficacy endpoint of the study will be the proportion of subjects that die prior to Day 60.The total study duration for a subject from screening to follow up visit is planned to be 62 days. In addition to the safety of VERU-111, an evaluation of the efficacy of VERU-111 on SARS-CoV-2 (COVID-19) compared to the placebo control will be evaluated as part of the Independent Data Monitoring Committee (IDMC).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 204
• Est. completion date: July 6, 2022
• Est. primary completion date: July 6, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

Inclusion Criteria:

• Provide informed consent from the subject or the subject's Legally Authorized Representative (LAR)

• Aged =18 years

• Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection confirmed by polymerase chain reaction (PCR) test

• Patients with a WHO Ordinal Scale for Clinical Improvement score of 4 at high risk for ARDS, must have at least one of the known comorbidities for being at high risk, such as, Asthma (moderate to severe), Chronic Lung Disease, Diabetes, Hypertension, Severe Obesity (BMI =40), 65 years of age or older, primarily reside in a nursing home or long-term care facility, or immunocompromised and patients with a WHO Ordinal Scale for Clinical Improvement score of 5 or 6 regardless of presence of comorbidities.

• WHO Ordinal Scale for Clinical Improvement score of 4 (Oxygen by mask or nasal prongs), 5 (Non-invasive ventilation or high-flow oxygen) or 6 (Intubation and mechanical ventilation)

• Peripheral capillary oxygen saturation (SpO2) = 94% on room air at screening. If patient is on oxygen therapy at the time of presentation for screening and the SpO2 levels were =94% prior to introduction to oxygen therapy with proper documentation example EMT notes or ER/ED notes, then the patient is considered to have met this inclusion criterion. If patient is on oxygen therapy at the time of presentation for screening and the SpO2 levels prior to introduction to oxygen therapy are unknown, the patient may be considered to have met this inclusion criterion if oxygen therapy is removed and the SpO2 levels fall to =94%, then the patient is considered to have met this inclusion criterion. However, removal of the oxygen therapy should only be done if it is considered medically reasonable

• Subjects must agree to follow doctor's recommendation for oxygen supplementation

• Subjects must agree to use acceptable methods of contraception:

• If female of childbearing potential or a male subject's partner could become pregnant, use acceptable methods of contraception from the time of the first administration of study medication until 6months following administration of the last dose of study medication. Acceptable methods of contraception are as follows: Condom with spermicidal foam/gel/film/cream/suppository [i.e., barrier method of contraception], surgical sterilization (vasectomy with documentation of azospermia) and a barrier method {condom used with spermicidal foam/gel/film/cream/suppository}, the female partner uses oral contraceptives (combination estrogen/progesterone pills), injectable progesterone or subdermal implants and a barrier method (condom used with spermicidal foam/gel/film/cream/suppository)

• If the female partner of a male subject has undergone documented tuballigation (female sterilization), a barrier method (condom used with spermicidal foam/gel/film/cream/suppository)should also be used

• If female partner of a male subject has undergone documented placement of an intrauterine device (IUD) or intrauterine system (IUS),a barrier method (condom with spermicidal foam/gel/film/cream/suppository)should also be used

• Subject is willing to comply with the requirements of the protocol through the end of the study

Exclusion Criteria:

• Known hypersensitivity or allergy to colchicine

• Pregnant or currently breast feeding

• Participation in any other clinical trial of an experimental treatment for COVID- 19. Convalescent plasma, dexamethasone and remdesivir are allowed in this study.

• Concurrent treatment with other experimental agents with actual or possible direct acting antiviral activity against COVID-19is prohibited <24 hours prior to study drug dosing(except standard of care). Remdesivir, dexamethasone and convalescent plasma are allowed in the study.

• Requiring ventilation + additional organ support - pressors, RRT, ECMO(WHO Ordinal Scale for Clinical Improvement - Score of 7). NOTE: short term (PRN) use of pressors is allowed

• Alanine Aminotransferase (ALT) or aspartate aminotransferase(AST) >3X upper limit of normal (ULN)

• Total bilirubin > ULN

• Creatinine clearance < 60 mL/min

• Documented medical history of liver disease, including but not limited to, prior diagnosis of hepatitis of any etiology, cirrhosis, portal hypertension, or confirmed or suspected esophageal varices

• Moderate to severe renal impairment

• Hepatic impairment

• History of hepatitis - (Hepatitis B and C) NOTE: treated and controlled hepatitis C is allowed

• Any comorbid disease or condition (medical or surgical) which might compromise the hematologic, cardiovascular, endocrine, pulmonary, renal, gastrointestinal, hepatic, or central nervous system; or other conditions that may interfere with the absorption, distribution, metabolism or excretion of study drug, or would place the subject at increased risk

• Participants must agree to refrain from prolonged exposure to the sun or agree to use at least SPF 50 on all exposed skin and protective clothing during prolonged sun exposure throughout participation in this study and/or treatment with VERU-111

Related Conditions & MeSH terms

• Infections
• SARS-CoV Infection
• Severe Acute Respiratory Syndrome

Intervention

Drug:
• VERU-111
Subjects in the VERU-111 treatment groups will receive standard of care, plus oral daily VERU-111 9mg for 21 days or until released from hospital.

Locations

Country	Name	City	State
Argentina	Center Sagrado Corazon	Buenos Aires
Argentina	Hospital De Alta Compleijdad Cuenca Alta Nestor Kirchner	Buenos Aires
Argentina	Hospital De Infecciosas "Dr. Francisco Javier Muniz"	Buenos Aires
Argentina	Hospital del Bicentenario de Esteban Echeverría	Buenos Aires
Argentina	Sanatorio Güemes	Buenos Aires
Brazil	Fundacao Pio XII - Hospital de Amor de Barretos	Barretos	Sao Paulo
Brazil	Faculdade de Medicina de Botucatu - UNESP	Botucatu
Brazil	Hospital Universitário São Francisco na Providencia de Deus	Bragança Paulista
Brazil	Hospital PUC Campinas	Campinas	Sao Paulo
Brazil	IPECC (Instituto De Pesquisa Clínica de Campinas)	Campinas
Brazil	Sociedade Hospital Angelina Caron	Campinas
Brazil	Santa Casa de Curitiba	Curitiba
Brazil	Complexo Hospitalar de Niteroi	Niteroi
Brazil	Hospital de Clínicas de Porto Alegre - Infectologia - Centro de Pesquisa Clínica	Porto Alegre
Brazil	Hospital Sao Luca Da PUCRS	Porto Alegre
Brazil	Hospital Universitario Cementino Fraga Filho	Rio De Janeiro
Brazil	IDOR - D'Or Institute for Research and Education	Sao Paulo
Brazil	Incor - Instituto do Coração do Hospital das Clínicas da FMUSP	Sao Paulo
Brazil	Fundação Faculdade Regional de Medicina de São José do Rio Preto	São Paulo
Brazil	Hospital Miguel Soeiro Sorocaba	Sorocaba
Bulgaria	MHAT Blagoevgrad AD Department of Infectious Diseases	Blagoevgrad
Bulgaria	Multiprofile Hospital for Active Treatment - Haskovo, Department of Infectious Diseases	Haskovo
Bulgaria	Multiprofile Hospital for Active Treatment - Dr. Atanas Dafovski AD, Kardzhali, Department of Pneumology and Phthisiatry, Dept. of Pneumology & Phthisiatry	Kardzhali
Bulgaria	Specialized hospital for active treatment of pulmonary diseases -Pernik EOOD, Pernik	Pernik
Bulgaria	University Multiprofile Hospital for Active Treatment "Pulmed" OOD Plovid Rheumatology	Plovdiv
Bulgaria	MHAT Bratan Shukerov,Pulmonology Department	Smolyan,
Bulgaria	Multiprofile Hospital for Active Treatment and Emergency Medicine	Sofia
Bulgaria	University Multiprofile Hospital for Active Treatment "Tsaritsa Yoanna-ISUL" EAD, Sofia,	Sofia
Bulgaria	University Multiprofile Hospital for Active Treatment "Professor Doctor Stoyan Kirkovich" AD, Stara Zagora, Clinic of Anaestheology and intensive care	Stara Zagora
Colombia	Fundación Hospital Universidad del Norte (Barranquilla)	Atlántico
Colombia	Clinica de la Costa (Barranquilla)	Barranquilla
Colombia	Fundación Cardioinfantil-Instituto de Cardiología	Bogotá
Colombia	Centro Medico Imbanaco de Cali S.A	Cali
Colombia	Sociedad Medica Rionegro- Clínica Somer (Rionegro)	Rionegro
Mexico	Hospital General de Culiacán	Culiacán
Mexico	Unidad Médica para la Salud Integral (UMSI)	San Nicolas de los Garza	Nuevo Leon
Mexico	Hospital General de Occidente	Zapopan
United States	University of North Carolina	Chapel Hill	North Carolina
United States	Atrium Health Carolinas Medical Center	Charlotte	North Carolina
United States	Velocity Clinical Research	Chula Vista	California
United States	Benchmark Research	Covington	Louisiana
United States	The Stern Cardiovascular Foundation, Inc.	Germantown	Tennessee
United States	Clinical Trial Network	Houston	Texas
United States	HD Research (Memorial Hermann - Memorial City Medical Center)	Houston	Texas
United States	HD Research (Memorial Hermann Southeast Hospital)	Houston	Texas
United States	St. Bernard's Medical Center	Jonesboro	Arkansas
United States	Velocity Clinical Research - San Diego	La Mesa	California
United States	Wellstar Research Institute	Marietta	Georgia
United States	Regional One Health	Memphis	Tennessee
United States	Westchester General Hospital, Research Department	Miami	Florida
United States	Inspira Medical Center Mullica Hill	Mullica Hill	New Jersey
United States	North Knoxville Medical Center	Powell	Tennessee
United States	Methodist Hospital	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	Honor Health	Scottsdale	Arizona
United States	James A. Haley Veterans Hospital	Tampa	Florida
United States	Holy Name Medical Center, Institute for Clinical Research	Teaneck	New Jersey
United States	Inspira Medical Center	Vineland	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Veru Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Bulgaria,  Colombia,  Mexico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy of Sabizabulin in the Treatment of SARS-CoV-2 Infection by Assessing Its Effect on the Proportion of Patients Who Died on Study.	Efficacy of VERU-111 in the treatment of SARS-Cov- 2 Infection by assessing its effect on the proportion of patients who die on study (prior to Day 60).	Day 60
Secondary	The Proportion of Subjects That Are Alive Without Respiratory Failure at Day 15, Day 22 and Day 29.	The proportion of subjects that are alive without respiratory failure at Day 15, Day 22 and Day 29. Respiratory failure is defined as endotracheal intubation and mechanical ventilation, extracorporeal membrane oxygenation, high-flow nasal cannula oxygen delivery, noninvasive positive pressure ventilation, clinical diagnosis of respiratory failure with initiation of none of these measures only when clinical decision making is driven solely by resource limitation.	Day 15, Day 22, Day 29